Several recent studies have shown that cardiovascular dysfunction may be an important complication of HIV infection, but the exact incidence of this problem, and the mechanism(s) by which it develops have not been defined. Evidence of increased reactive oxygen intermediates (R0I's) has been found in blood and tissues of HIV patients and animal models of retroviral infection; these conditions have been implicated in HIV viral activation, cytokine production, and immune system dysfunction. As a free radical and potent oxidant (particularly when combined with superoxide anion), NO has recently been implicated in AIDS-related neurotoxicity and dementia. It is therefore possible that important changes in NO production or destruction processes may play a role in retroviral immunopathogenesis, particularly in cardiovascular complications. The long term objectives are to determine the mechanism(s) of retrovirus related cardiovascular complications, define the role(s) of NO in these changes, and examine how can they be prevented or resolved. A relevant and well-documented mouse model of retroviral infection that has been shown to develop cardiac damage during infection will be studied. In vivo cardiac dysfunction will be related to cardiac oxidative damage during retroviral infection, and changes in balance between NO production and destruction pathways will be examined during immunopathogenesis and cardiac impairment. The investigators will also design and test rational strategies to intervene. In related investigations they will determine the relation of endogenous NO in expired air to cardiovascular and pulmonary complications in HIV infected patients. These studies will provide important new information regarding the mechanisms of cardiac dysfunction in retroviral infection, and provide important new insights and strategies for an emerging problem. (End of Abstract)